This invention relates to anti-cancer therapy, particularly for the treatment of solid tumors.
Cancer accounts for one fifth of the total mortality in the United States and is the second leading cause of death. One effective anti-cancer therapy is chemotherapy. However, in the treatment of solid tumors (e.g., tumors in the lung, colon, and breast), efficient treatment is hindered by the difficulty in penetrating the tumor mass with anti-cancer agents (Jain, Sci. Amer. 271: 58-65, 1994). Hence, the identification of a means by which to facilitate the delivery of therapeutic agents to the cancer site would enhance the effectiveness of anti-cancer therapies.
We have discovered methods and reagents for increasing the sensitivity of cancers to therapy, and particularly chemotherapy. These methods and reagents are useful in treating cancers, particularly solid tumors.
Accordingly, in a first aspect, the invention features a method for treating a cancer in a mammal that involves administering relaxin and an anti-cancer therapy to the mammal, the relaxin and the anti-cancer therapy being administered at dosages which together are sufficient to destroy, slow, or arrest the cancer. In various preferred embodiments of this aspect of the invention, the relaxin is administered either prior to the administration of the anti-cancer therapy or simultaneously with the administration of the anti-cancer therapy. In another preferred embodiment, the method further involves administration of xcex3-interferon.
In a second aspect, the invention features a method for treating a cancer in a mammal that involves administering xcex3-interferon and an anti-cancer therapy to the mammal, the xcex3-interferon and the anti-cancer therapy being administered at dosages which together are sufficient to destroy, slow, or arrest the cancer. In various preferred embodiments of this aspect of the invention. the xcex3-interferon is administered either prior to the administration of the anti-cancer therapy or simultaneously with the administration of the anti-cancer therapy. In another preferred embodiment, the method further involves administration of relaxin.
In preferred embodiments of both the first and second aspects of the invention, the anti-cancer therapy includes a biotherapeutic agent, for example, a chemotherapeutic agent. And in other preferred embodiments, the mammal is a human; and the cancer is a solid tumor, for example, a solid tumor in a tissue selected from the group consisting of brain, kidney, liver, nasopharyngeal cavity, thyroid, skin, central nervous system, ovary, breast, prostate, colon, rectum, uterus, cervix, endometrium, lung, bladder, pancreas, and lymph node.
In related aspect, the invention features a method for treating a cancer in a mammal that involves administering to the mammal a tissue tensile modulus-reducing compound and an anti-cancer therapy, the compound and the anti-cancer therapy being administered at dosages which together are sufficient to destroy, slow, or arrest the cancer.
In yet another related aspect, the invention features a method for treating a cancer in a mammal that involves administering to the mammal a compound that increases the hydraulic conductance of the cancer and an anti-cancer therapy, the compound and the anti-cancer therapy being administered at dosages which together are sufficient to destroy, slow, or arrest the cancer.
In a final related aspect, the invention features a method for treating a cancer in a mammal that involves administering to the mammal a compound that increases collagen turnover or decreases collagen formation at or near the cancer and an anti-cancer therapy, the compound and the anti-cancer therapy being administered at dosages which together are sufficient to destroy, slow, or arrest the cancer.
In various preferred embodiments of the above related aspects, the anti-cancer therapy includes a biotherapeutic agent, for example, a chemotherapeutic agent; the mammal is a human; the cancer is a solid tumor; and the compound is either relaxin or xcex3-interferon, or both.
As used herein, by xe2x80x9ccancerxe2x80x9d or xe2x80x9cneoplasmxe2x80x9d is meant any abnormal proliferation of cells, which may be benign or malignant, and which includes solid tumors. Solid tumors may occur in a variety of tissues including, without limitation, the brain, kidney, liver, nasopharyngeal cavity, thyroid, skin, central nervous system, ovary, breast, prostate, colon, rectum, uterus, cervix, endometrium, lung, bladder, pancreas, and lymph node.
By xe2x80x9canti-cancer therapyxe2x80x9d is meant any therapy that destroys a cancer cell, or slows, arrests, or reverses the growth of a cancer cell. Anti-cancer therapies include, without limitation, radiation therapy (radiotherapy), chemotherapy, or a combination of these therapies.
By xe2x80x9cchemotherapyxe2x80x9d is meant the use of a chemical agent to destroy a cancer cell, or to slow, arrest, or reverse the growth of a cancer cell.
By xe2x80x9cbiotherapeutic agentxe2x80x9d is meant a substituted or unsubstituted peptide, polypeptide, virus cell, glycan, or combination thereof, which may be used to destroy a cancer cell, or to slow, arrest, or reverse the growth of a cancer cell.
By xe2x80x9cchemotherapeutic agentxe2x80x9d is meant a chemical that may be used to destroy a cancer cell, or to slow, arrest, or reverse the growth of a cancer cell. Chemotherapeutic agents include, without limitation, asparaginase, bleomycin, busulfan carmustine (commonly referred to as BCNU), chlorambucil, cladribine (commonly referred to as 2-CdA), irinotecan (CPT-11), cyclophosphamide, cytarabine (commonly referred to as Ara-C), dacarbazine, daunorubicin, dexamethasone, doxorubicin (commonly referred to as Adriamycin), etoposide, fludarabine, 5-fluorouracil (commonly referred to as 5FU), hydroxyurea, idarubicin, ifosfamide, interferon-xcex1 (native or recombinant), levamisole, lomustine (commonly referred to as CCNU), mechlorethamine (commonly referred to as nitrogen mustard), melphalan, mercaptopurine, methotrexate, mitomycin, mitoxantrone, paclitaxel, pentostatin, prednisone, procarbazine, tamoxifen, taxol-related compounds, 6-thiogaunine, topotecan, vinblastine, and vincristine.
By xe2x80x9cresponsivexe2x80x9d is meant that a cell is destroyed by an anti-cancer therapy, or that the growth of a cell is slowed, arrested, or reversed by an anti-cancer therapy. The growth may be measured by any standard technique including, for example, cell count, measurement with calipers, or weight. Preferably, the growth of the cancer is reversed such that the cancer is at least 50% smaller than the cancer prior to therapy. Most preferably, the cancer is destroyed by the therapy.
By a xe2x80x9ctissue tensile modulus-reducing compoundxe2x80x9d is meant a compound that reduces the tensile modulus (i.e., the Young""s modulus, or the coefficient of the strain in the linear stress to strain relation) of tissue deformed by the presence of a cancer.
Other features and advantages of the invention will be apparent from the following detailed description and from the claims.